Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.     

A queuing model for distributed scheduling in IEEE 802.16 wireless mesh networks

The IEEE 802.16 standard for wireless broadband networks includes the mesh mode in its specifications, where network nodes interact to deliver packets from a client to a remote destination through intermediate nodes. This paper presents a study of the capacity of IEEE 802.16 wireless networks in mesh mode by using M/G/1/L queuing model that represents each network node by incorporating the features of the standard in order to calculate the average delay and throughput in the node. An iterative method integrates the calculation results at each node, obtaining the end‐to‐end delay from any node of the mesh to the Base Station. Because of multiple hops, a node far from the Base Station may have its flows damaged. To minimize this problem, we propose a criterion for a fair distribution of resources. We show the numerical results of the model which indicate a good fit when compared with simulation results. Copyright © 2013 John Wiley & Sons, Ltd.     

A socially inspired energy feedback technology: challenges in a developing scenario

Raising awareness of the environmental impact of energy generation and consumption has been a recent concern of contemporary society worldwide. Underlying the awareness of energy consumption is an intricate network of perception and social interaction that can be mediated by technology. In this paper we argue that issues regarding energy, environment and technology are very much situated and involve tensions of sociocultural nature. This exploratory investigation addresses the subject by introducing the design of a Socially-inspired Energy Eco-Feedback Technology (SEET), which is composed of an interactive system to trigger and mediate collective savings and a tangible device as a public feedback. Results of an evaluation situated in the context of a school in a socially disadvantaged area in Brazil are discussed, shedding light on the sociocultural aspects related to the subject. The role of the SEET to motivate energy awareness collectively among the social group is assessed, as well as the design characteristics that contributed to that. Outcomes bring to light social aspects and dynamics that would hardly have been predicted, evidencing critical factors related to a socially inspired design approach in the energy awareness domain.     

Synthesis and Evaluation of Water‐Soluble Prodrugs of Ursodeoxycholic Acid (UDCA), an Anti‐apoptotic Bile Acid

Ursodeoxycholic acid (UDCA) is a bile acid with demonstrated anti‐apoptotic activity in both in vitro and in vivo models. However, its utility is hampered by limited aqueous solubility. As such, water‐soluble prodrugs of UDCA could have an advantage over the parent bile acid in indications where intravenous administration might be preferable, such as decreasing damage from stroke or acute kidney injury. Five phosphate prodrugs were synthesized, including one incorporating a novel phosphoryloxymethyl carboxylate (POMC) moiety. These prodrugs were highly water‐soluble, but showed significant differences in chemical stability, with oxymethylphosphate prodrugs being the most unstable. In a series of NMR experiments, the POMC prodrug was bioactivated to UDCA by alkaline phosphatase (AP) faster than a prodrug containing a phosphate directly attached to the alcohol at the 3‐position of UDCA. Both of these prodrugs showed significant anti‐apoptotic activity in a series of in vitro assays, although the POMC prodrug required the addition of AP for activity, while the other compound was active without exogenous AP.     

Utilization of electrochemical impedance spectroscopy for monitoring bornite (Cu5FeS4) oxidation by Acidithiobacillus ferrooxidans

In this work, the monitoring of the bacterial and chemical dissolution of bornite was evaluated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS); the mineral surface was examined using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The analysis of CV results allowed attributing the different peaks observed in both direct and reverse potential scanning to the oxidation of bornite to a secondary covellite and its reduction via different non stoichiometric copper sulphides intermediaries. EIS data for bornite were obtained in control medium up to 78 h of immersion, when a cellular suspension of A. ferrooxidans was added and the experiments continued up to a 192 h of test. The EIS response was different when bacteria were added in the beginning of the test or after some hours of immersion in acid solution. The experiments were performed in different cell configurations and a model of the electrode/electrolyte interface. The correspondent equivalent electrical circuit was used to fit impedance spectra for all studied conditions. A common equivalent circuit used for corrosion processes where anodic (degradation of the mineral) and cathodic (oxygen reduction) reactions occur in parallel, together film and biofilm formation was proposed.     

Accessibility and interoperability in e-government systems: outlining an inclusive development process

The multidisciplinary nature of e-government demands a research agenda that includes issues related to social inclusion, universal accessibility, interoperability, privacy, security, and citizen participation, to name a few. Understanding the underlying cultural context, the involvement of citizens in the proposal and evaluation of services, and the promotion of quality in use are aspects that need special consideration in the development of systems to support government. This paper provides an outline for a process model for promoting the identification and specification of accessible e-government services with the participation of the interested parties. A socially shared perspective is adopted toward the comprehension of the involved problems and the elaboration of potential solutions. The proposed model is a result of practice in the domain, using organizational semiotics artifacts to stimulate participation and discussion.     

In Situ analysis of CO2 laser irradiation on controlling progression of erosive lesions on dental enamel

The present study aimed to evaluate in situ the effect of CO₂ laser irradiation to control the progression of enamel erosive lesions. Fifty‐six slabs of bovine incisors enamel (5 × 3 × 2.5 mm³) were divided in four distinct areas: (1) sound (reference area), (2) initial erosion, (3) treatment (irradiated or nonirradiated with CO₂ laser), (4) final erosion (after in situ phase). The initial erosive challenge was performed with 1% citric acid (pH = 2.3), for 5 min, 2×/day, for 2 days. The slabs were divided in two groups according to surface treatment: irradiated with CO₂ laser (λ = 10.6 µm; 0.5 W) and nonirradiate. After a 2‐day lead‐in period, 14 volunteers wore an intraoral palatal appliance containing two slabs (irradiated and nonirradiated), in two intraoral phases of 5 days each. Following a cross‐over design during the first intraoral phase, half of the volunteers immersed the appliance in 100 mL of citric acid for 5 min, 3×/day, while other half of the volunteers used deionized water (control). The volunteers were crossed over in the second phase. Enamel wear was determined by an optical 3D profilometer. Three‐way ANOVA for repeated measures revealed that there was no significant interaction between erosive challenge and CO₂ laser irradiation (P = 0.419). Erosive challenge significantly increased enamel wear (P = 0.001), regardless whether or not CO₂ laser irradiation was performed. There was no difference in enamel wear between specimens CO₂‐laser irradiated and non‐irradiated (P = 0.513). Under intraoral conditions, CO₂ laser irradiation did not control the progression of erosive lesions in enamel caused by citric acid. Microsc. Res. Tech. 77:586–593, 2014. © 2014 Wiley Periodicals, Inc.     

Isolation of an acetyl-CoA synthetase gene (ZbACS2) from Zygosaccharomyces bailii

A gene homologous to Saccharomyces cerevisiae ACS genes, coding for acetyl-CoA synthetase, has been cloned from the yeast Zygosaccharomyces bailii ISA 1307, by using reverse genetic approaches. A probe obtained by PCR amplification from Z. bailii DNA, using primers derived from two conserved regions of yeast ACS proteins, RIGAIHSVVF (ScAcs1p; 210-219) and RVDDVVNVSG (ScAcs1p; 574-583), was used for screening a Z. bailii genomic library. Nine clones with partially overlapping inserts were isolated. The sequenced DNA fragment contains a complete ORF of 2027 bp (ZbACS2) and the deduced polypeptide shares significant homologies with the products of ACS2 genes from S. cerevisiae and Kluyveromyces lactis (81% and 82% identity and 84% and 89% similarity, respectively). Phylogenetic analysis shows that the sequence of Zbacs2 is more closely related to the sequences from Acs2 than to those from Acs1 proteins. Moreover, this analysis revealed that the gene duplication producing Acs1 and Acs2 proteins has occurred in the common ancestor of S. cerevisiae, K. lactis, Candida albicans, C. glabrata and Debaryomyces hansenii lineages. Additionally, the cloned gene allowed growth of S. cerevisiae Scacs2 null mutant, in medium containing glucose as the only carbon and energy source, indicating that it encodes a functional acetyl-CoA synthetase. Also, S. cerevisiae cells expressing ZbACS2 have a shorter lag time, in medium containing glucose (2%, w/v) plus acetic acid (0.1-0.35%, v/v). No differences in cell response to acetic acid stress were detected both by specific growth and death rates. The mode of regulation of ZbACS2 appears to be different from ScACS2 and KlACS2, being subject to repression by a glucose pulse in acetic acid-grown cells.     

Key role of the resin layer thickness in the lability of complexes measured by DGT

Analysis of the dynamic features of diffusion gradients in thin film devices (DGT) indicates that the penetration of complexes into the resin layer dramatically increases their lability. This should be taken into account when interpreting DGT measurements in terms of the dynamics of solution speciation. The experimental accumulation of Cd by DGT sensors in Cd-NTA systems confirmed these theoretical analyses. A computational code, which allows a rigorous digital simulation of the diffusion-reaction processes in the gel and resin layers, was used to model the results and to demonstrate the effect of the complex penetration into the resin layer on the lability degree. These findings suggest that DGT renders all complexes much more labile than if the resin-diffusive gel interface was considered as a perfect planar sink, explaining why DGT often measures a high proportion of the metal in a natural water. This information is relevant since some studies have stressed the importance of labile complexes as a source of bioaccumulated metal.